Temporal Dynamics and (Para)Clinical Factors Associated With (Long) Viral RNA Shedding in COVID-19 Nonhospitalized Individuals – The COVID-HOME Study

Understanding temporal patterns and determinants of RNA shedding is important to comprehend SARS-CoV-2 transmission and improve biosafety/isolation guidelines. Nonhospitalized SARS-CoV-2-infected individuals and household members were enrolled between March 2020 and June 2021 and followed prospectively ≥ 3 weeks during acute disease and at 3-, 6-, 12-, and 18-months to obtain (para)clinical data and biospecimens. Flow cytometry-based surrogate assay (FlowSA) detected viable SARS-CoV-2. Determinants of long RNA shedding ( ≥ 21 days) were investigated. RNA shedding median duration was 14 days (IQR 8.0–21.0) for nasopharyngeal/throat (NPT) and 7 days (IQR 1.0–27.0) for feces— but 20 days (IQR 7.0–27.8) when excluding individuals positive at a single timepoint (25.2%). Among 17 NPT long shedders with FlowSA results, 12 (70.6%) demonstrated viable virus. NPT long shedding was independently positively associated with endocrine disease and chills. Fecal long shedding was independently inversely associated with age, female sex, and fatigue, but positively with vomiting. No associations with long-term COVID-19-related complaints were observed. Finally, fecal long shedders demonstrated higher anti-spike(S1) IgG levels over 18-month follow-up than non-long shedders (p = 0.006). (Long) SARS-CoV-2 RNA shedding in NPT and feces associates with age and acute—but not prolonged—symptoms. The roles of prolonged infectious shedding and fecal shedding in transmission and immunity remain unclear.